Our objective is to determine the long-term sequelae of the administration of opiates and other drugs of abuse to rodent parents, prior to mating, upon the development of subsequent progeny and to elucidate possible mechanisms for this effect. Our previous studies have demonstrated that premating administration of opioids to male or female rodents results in an attenuation of analgesic response among first generation offspring and alterations in both the physical and the behavioral development of subsequent progeny. Although the mechanism(s) for the tenaciousness of the premating exposure to opiates is not presently understood, both neuroendocrine and genetic factors are implicated in the findings to date. Studies will more fully examine the sequelae of exposure of the male mouse parent upon his subsequent offspring. To investigate the role of genetic factors, selective inbreeding studies will be expanded. The character of the behavioral changes observed to date suggest that the opioid-derived progeny possess alterations in their responsiveness to stress. Neuroendocrine studies will explore the nature of these changes. Investigations utilizing drugs which do not possess the dependence-producing properties of the opioids will determine whether the premating influence is limited to drugs which possess opioid-like activity or may be extended to other classes of centrally active compounds.